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  • 1
    In: Frontiers in Endocrinology, Frontiers Media SA, Vol. 13 ( 2022-9-6)
    Abstract: Metabolic syndrome (MetS) is one of the most important medical problems around the world. Identification of patient´s singular characteristic could help to reduce the clinical impact and facilitate individualized management. This study aimed to categorize MetS patients using phenotypical and clinical variables habitually collected during health check-ups of individuals considered to have high cardiovascular risk. The selected markers to categorize MetS participants included anthropometric variables as well as clinical data, biochemical parameters and prescribed pharmacological treatment. An exploratory factor analysis was carried out with a subsequent hierarchical cluster analysis using the z-scores from factor analysis. The first step identified three different factors. The first was determined by hypercholesterolemia and associated treatments, the second factor exhibited glycemic disorders and accompanying treatments and the third factor was characterized by hepatic enzymes. Subsequently four clusters of patients were identified, where cluster 1 was characterized by glucose disorders and treatments, cluster 2 presented mild MetS, cluster 3 presented exacerbated levels of hepatic enzymes and cluster 4 highlighted cholesterol and its associated treatments Interestingly, the liver status related cluster was characterized by higher protein consumption and cluster 4 with low polyunsaturated fatty acid intake. This research emphasized the potential clinical relevance of hepatic impairments in addition to MetS traditional characterization for precision and personalized management of MetS patients.
    Type of Medium: Online Resource
    ISSN: 1664-2392
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2592084-4
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  • 2
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 14 ( 2023-5-4)
    Abstract: Inborn errors of immunity (IEI) are a heterogeneous group of diseases caused by intrinsic defects of the immune system. Estimating the immune competence of immunocompromised patients for an infection risk assessment or after SARS-CoV-2 vaccination constituted a challenge. Methods The aim of this study was to determine the humoral responses of patients with IEI through a comprehensive analysis of specific receptor-binding domain-positive (RBD+) IgG+ memory B cells (MBCs) by flow cytometry, together with routine S-specific IgG antibodies and QuantiFERON SARS-CoV-2 (T-cell response), before the vaccine and 3 weeks after a second dose. Results and discussion We first analyzed the percentage of specific RBD+ IgG+ MBCs in healthy healthcare workers. Within the control group, there was an increase in the percentage of specific IgG+ RBD+ MBCs 21 days after the second dose, which was consistent with S-specific IgG antibodies.Thirty-one patients with IEI were included for the pre- and post-vaccination study; IgG+ RBD+ MBCs were not evaluated in 6 patients due to an absence of B cells in peripheral blood. We detected various patterns among the patients with IEI with circulating B cells (25, 81%): an adequate humoral response was observed in 12/25, consider by the detection of positive S-specific IgG antibodies and the presence of specific IgG+ RBD+ MBCs, presenting a positive T-cell response; in 4/25, very low S-specific IgG antibody counts correlated with undetectable events in the IgG+ RBD+ MBC compartment but with positive cellular response. Despite the presence of S-specific IgG antibodies, we were unable to detect a relevant percentage of IgG+ RBD+ MBCs in 5/25; however, all presented positive T-cell response. Lastly, we observed a profound failure of B and T-cell response in 3 (10%) patients with IEI, with no assessment of S-specific IgG antibodies, IgG+ RBD+ MBCs, and negative cellular response. The identification of specific IgG+ RBD+ MBCs by flow cytometry provides information on different humoral immune response outcomes in patients with IEI and aids the assessment of immune competence status after SARS-CoV-2 mRNA vaccine (BNT162b2), together with S-specific IgG antibodies and T-cell responses.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2606827-8
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  • 3
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 13 ( 2023-4-28)
    Abstract: Metastatic breast cancer (mBC) causes nearly all BC-related deaths. Next-generation sequencing (NGS) technologies allow for the application of personalized medicine using targeted therapies that could improve patients’ outcomes. However, NGS is not routinely used in the clinical practice and its cost induces access-inequity among patients. We hypothesized that promoting active patient participation in the management of their disease offering access to NGS testing and to the subsequent medical interpretation and recommendations provided by a multidisciplinary molecular advisory board (MAB) could contribute to progressively overcome this challenge. We designed HOPE (SOLTI-1903) breast cancer trial, a study where patients voluntarily lead their inclusion through a digital tool (DT). The main objectives of HOPE study are to empower mBC patients, gather real-world data on the use of molecular information in the management of mBC and to generate evidence to assess the clinical utility for healthcare systems. Trial design After self-registration through the DT, the study team validates eligibility criteria and assists patients with mBC in the subsequent steps. Patients get access to the information sheet and sign the informed consent form through an advanced digital signature. Afterwards, they provide the most recent (preferably) metastatic archival tumor sample for DNA-sequencing and a blood sample obtained at the time of disease progression for ctDNA analysis. Paired results are reviewed by the MAB, considering patient’s medical history. The MAB provides a further interpretation of molecular results and potential treatment recommendations, including ongoing clinical trials and further (germline) genetic testing. Participants self-document their treatment and disease evolution for the next 2 years. Patients are encouraged to involve their physicians in the study. HOPE also includes a patient empowerment program with educational workshops and videos about mBC and precision medicine in oncology. The primary endpoint of the study was to describe the feasibility of a patient-centric precision oncology program in mBC patients when a comprehensive genomic profile is available to decide on a subsequent line of treatment. Clinical trial registration www.soltihope.com , identifier NCT04497285.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2649216-7
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  • 4
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 6 ( 2015)
    Type of Medium: Online Resource
    ISSN: 1664-3224
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2015
    detail.hit.zdb_id: 2606827-8
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  • 5
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 12 ( 2022-3-22)
    Abstract: Most molecular-based published studies on breast cancer do not adequately represent the unique and diverse genetic admixture of the Latin American population. Searching for similarities and differences in molecular pathways associated with these tumors and evaluating its impact on prognosis may help to select better therapeutic approaches. Patients and Methods We collected clinical, pathological, and transcriptomic data of a multi-country Latin American cohort of 1,071 stage II-III breast cancer patients of the Molecular Profile of Breast Cancer Study (MPBCS) cohort. The 5-year prognostic ability of intrinsic (transcriptomic-based) PAM50 and immunohistochemical classifications, both at the cancer-specific (OSC) and disease-free survival (DFS) stages, was compared. Pathway analyses (GSEA, GSVA and MetaCore) were performed to explore differences among intrinsic subtypes. Results PAM50 classification of the MPBCS cohort defined 42·6% of tumors as LumA, 21·3% as LumB, 13·3% as HER2E and 16·6% as Basal. Both OSC and DFS for LumA tumors were significantly better than for other subtypes, while Basal tumors had the worst prognosis. While the prognostic power of traditional subtypes calculated with hormone receptors (HR), HER2 and Ki67 determinations showed an acceptable performance, PAM50-derived risk of recurrence best discriminated low, intermediate and high-risk groups. Transcriptomic pathway analysis showed high proliferation (i.e. cell cycle control and DNA damage repair) associated with LumB, HER2E and Basal tumors, and a strong dependency on the estrogen pathway for LumA. Terms related to both innate and adaptive immune responses were seen predominantly upregulated in Basal tumors, and, to a lesser extent, in HER2E, with respect to LumA and B tumors. Conclusions This is the first study that assesses molecular features at the transcriptomic level in a multicountry Latin American breast cancer patient cohort. Hormone-related and proliferation pathways that predominate in PAM50 and other breast cancer molecular classifications are also the main tumor-driving mechanisms in this cohort and have prognostic power. The immune-related features seen in the most aggressive subtypes may pave the way for therapeutic approaches not yet disseminated in Latin America. Clinical Trial Registration ClinicalTrials.gov (Identifier: NCT02326857).
    Type of Medium: Online Resource
    ISSN: 2234-943X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2649216-7
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  • 6
    In: Frontiers in Nutrition, Frontiers Media SA, Vol. 9 ( 2022-9-29)
    Abstract: Carotenoid intake has been reported to be associated with improved cardiovascular health, but there is little information on actual plasma concentrations of these compounds as biomarkers of cardiometabolic risk. The objective was to investigate the association between circulating plasma carotenoids and different cardiometabolic risk factors and the plasma fatty acid profile. This is a cross-sectional evaluation of baseline data conducted in a subcohort (106 women and 124 men) of an ongoing multi-factorial lifestyle trial for primary cardiovascular prevention. Plasma concentrations of carotenoids were quantified by liquid chromatography coupled to mass spectrometry. The associations between carotenoid concentrations and cardiometabolic risk factors were assessed using regression models adapted for interval-censored variables. Carotenoid concentrations were cross-sectionally inversely associated with serum triglyceride concentrations [−2.79 mg/dl (95% CI: −4.25, −1.34) and −5.15 mg/dl (95% CI: −7.38, −2.93), p -values = 0.0002 and & lt;0.00001 in women and men, respectively], lower levels of plasma saturated fatty acids [−0.09% (95% CI: −0.14, −0.03) and −0.15 % (95% CI: −0.23, −0.08), p -values = 0.001 and 0.0001 in women and men, respectively], and higher levels of plasma polyunsaturated fatty acids [(0.12 % (95% CI: −0.01, 0.25) and 0.39 % (95% CI: 0.19, 0.59), p -values = 0.065 and 0.0001 in women and men, respectively] in the whole population. Plasma carotenoid concentrations were also associated with higher plasma HDL-cholesterol in women [0.47 mg/dl (95% CI: 0.23, 0.72), p -value: 0.0002], and lower fasting plasma glucose in men [−1.35 mg/dl (95% CI: −2.12, −0.59), p -value: 0.001].
    Type of Medium: Online Resource
    ISSN: 2296-861X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2776676-7
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  • 7
    In: Frontiers in Nutrition, Frontiers Media SA, Vol. 9 ( 2022-7-14)
    Abstract: Helping consumers to improve the nutritional quality of their diet is a key public health action to prevent cardiovascular diseases (CVDs). The modified version of the Food Standard Agency Nutrient Profiling System Dietary Index (FSAm-NPS DI) underpinning the Nutri-Score front-of-pack label has been used in public health strategies to address the deleterious consequences of poor diets. This study aimed to assess the association between the FSAm-NPS DI and some CVD risk factors including body mass index (BMI), waist circumference, plasma glucose levels, triglyceride levels, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, and diastolic and systolic blood pressure. Materials and Methods Dietary intake was assessed at baseline and after 1 year of follow-up using a 143-item validated semi-quantitative food-frequency questionnaire. Dietary indices based on FSAm-NPS applied at an individual level were computed to characterize the diet quality of 5,921 participants aged 55–75 years with overweight/obesity and metabolic syndrome from the PREDIMED-plus cohort. Associations between the FSAm-NPS DI and CVD risk factors were assessed using linear regression models. Results Compared to participants with a higher nutritional quality of diet (measured by a lower FSAm-NPS DI at baseline or a decrease in FSAm-NPS DI after 1 year), those participants with a lower nutritional quality of diet (higher FSAm-NPS DI or an increase in score) showed a significant increase in the levels of plasma glucose, triglycerides, diastolic blood pressure, BMI, and waist circumference (β coefficient [95% confidence interval]; P for trend) (1.67 [0.43, 2.90]; & lt;0.001; 6.27 [2.46, 10.09]; & lt;0.001; 0.56 [0.08, 1.05]; 0.001; 0.51 [0.41, 0.60] ; & lt;0.001; 1.19 [0.89, 1.50]; & lt;0.001, respectively). No significant associations in relation to changes in HDL and LDL-cholesterol nor with systolic blood pressure were shown. Conclusion This prospective cohort study suggests that the consumption of food items with a higher FSAm-NPS DI is associated with increased levels of several major risk factors for CVD including adiposity, fasting plasma glucose, triglycerides, and diastolic blood pressure. However, results must be cautiously interpreted because no significant prospective associations were identified for critical CVD risk factors, such as HDL and LDL-cholesterol, and systolic blood pressure.
    Type of Medium: Online Resource
    ISSN: 2296-861X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2776676-7
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  • 8
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 9 ( 2019-4-26)
    Type of Medium: Online Resource
    ISSN: 2234-943X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2019
    detail.hit.zdb_id: 2649216-7
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  • 9
    In: Frontiers in Cardiovascular Medicine, Frontiers Media SA, Vol. 9 ( 2022-7-4)
    Abstract: Atrial fibrillation (AF) increases the risk of ischemic stroke in asymptomatic individuals and may be the underlying cause of many cryptogenic strokes. We aimed to test the usefulness of candidate blood-biomarkers related to AF pathophysiology in two prospective cohorts representative of those populations. Methods Two hundred seventy-four subjects aged 65–75 years with hypertension and diabetes from the AFRICAT cohort, and 218 cryptogenic stroke patients aged & gt;55 years from the CRYPTO-AF cohort were analyzed. AF was assessed by 4 weeks of monitoring with a wearable Holter device (NuuboTM™). Blood was collected immediately before monitoring started. 10 candidate biomarkers were measured by automated immunoassays (Roche, Penzberg) in the plasma of all patients. Univariate and logistic regression analyses were performed in each cohort separately. Results Atrial fibrillation detection rate was 12.4% (AFRICAT cohort) and 22.9% (CRYPTO-AF cohort). 4 biomarkers were significantly increased in asymptomatic individuals with AF [Troponin-T, Angiopoietin-2 (Ang-2), Endocan, and total N-terminal pro-B type natriuretic peptide (NT-proBNP)] and 7 biomarkers showed significantly higher concentrations in cryptogenic stroke patients with AF detection [growth differentiation factor 15, interleukin 6, Troponin-T, Ang-2, Bone morphogenic protein 10, Dickkopf-related protein 3 (DKK-3), and total NT-proBNP] . The models including Ang-2 and total NT-proBNP [AUC 0.764 (0.665–0.863)], and Ang-2 and DKK-3 [AUC = 0.733 (0.654–0.813)] , together with age and sex, showed the best performance to detect AF in high-risk asymptomatic individuals, and in cryptogenic stroke patients, respectively. Conclusion Blood-biomarkers, in particular, total NT-proBNP, DKK-3, and Ang-2, were associated with AF reflecting two mechanistically different pathways involved in AF pathophysiology (AF stretch and vascular changes). The combination of these biomarkers could be useful in AF screening strategies in the primary care setting and also for searching AF after cryptogenic stroke.
    Type of Medium: Online Resource
    ISSN: 2297-055X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2781496-8
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  • 10
    In: Frontiers in Pediatrics, Frontiers Media SA, Vol. 10 ( 2022-4-1)
    Abstract: Sustained social withdrawal is a key indicator of child emotional distress and a risk factor for psychological development. Preterm infants have a higher probability of developing sustained social withdrawal than infants born full-term during their first year. Objective To compare the effect of a behavioral guidance intervention to that of routine pediatric care on sustained social withdrawal behavior in preterm infants. Design Multicenter randomized clinical trial. Participants Ninety nine moderate and late preterm newborns and their parents were recruited and randomized into two groups, i.e., Intervention ( n = 49) and Control ( n = 50). Both groups attended medical check-ups at 2, 6 and 12 months and were assessed with the Alarm Distress Baby Scale. The intervention group received a standardized behavioral intervention if the neonatologist detected sustained social withdrawal. Also, parents filled out the Edinburgh Postnatal Depression Scale, the modified-Perinatal Posttraumatic Stress Disorder Questionnaire, and the Impact of Event Scale-revised. Results At baseline, the prevalence of withdrawal was 4.0% (95% CI: 0.03–14.2) for the control group and 22.4% (95% CI: 13.0–35.9) for the intervention group [OR = 0.22, p = 0.028 (95% CI =0.06–0.84)]. At 6 months, the prevalence was 10.0% (95% CI: 3.9–21.8) for the control group and 6.1% (95% CI: 2.1–16.5) for the intervention group [OR = 2.09, p = 0.318 (95% CI = 0.49–8.88)]. At 12 months, the prevalence was 22.0% (95% CI: 12.8–35.2) for the control group and 4.1% (95% CI: 1.1–13.7) for the intervention group [OR = 6.63, p = 0.018 (95% CI = 1.39–31.71)]. Logistic generalized estimating equation models were performed. The pooled crude OR (considering diagnosis at 6 and 12 months) was 3.54 [ p = 0.022 (95% CI = 1.20–10.44); Cohen's d= 0.70]. In the case of pooled adjusted OR, the model considered diagnosis (0 = Withdrawal, 1 = Normal) as the dependent variable, time of evaluation (1= 6 months, 2 = 12 months) and group (0 = Control, 1 = Experimental) as factors. In this case, the pooled adjusted OR was 3.57 [ p = 0.022 (95% CI = 1.20–10.65); Cohen's d = 0.70]. Conclusion Assessment and intervention of sustained social withdrawal in preterm infants via standardized instruments benefits families by reducing its prevalence, and possible associated negative outcomes. Clinical Trial Registration ClinicalTrials.gov; https://clinicaltrials.gov/ct2/show/NCT03212547 , identifier: NCT03212547.
    Type of Medium: Online Resource
    ISSN: 2296-2360
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2711999-3
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